Pathology

• Definitive decision making regarding patient management should be guided by pathological diagnosis of conventional preoperative biopsies (including core biopsy) and/or fine needle aspiration cytology (FNAC).
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• Specimens for the diagnosis of a head and neck cancer should be clearly labelled as urgent and include all relevant clinical & staging information on the accompanying specimen request form.
  
  
• The laboratory should place particular care on the handling of biopsy / FNA specimens due to the increased requirement for tissue preservation to ensure sufficient material is available for ancillary testing (see below).
  
  
• Diagnostic terminology used in pathology reports should be in line with the current WHO classification of head and neck tumours. This includes information on grading where appropriate.

• Report resection specimens and neck dissection specimens in accordance with the relevant and most recent RCPath minimum dataset. Consider using reporting proformas as they are useful to ensure all core data items are included.
  
  
• Fully submerge all resection specimens in 10 per cent neutral buffered formalin in at least four times the volume of the specimen as soon as possible. On the request form clearly indicate the site, laterality, clinical stage and nature of each specimen. Correct orientation of the specimen is of paramount importance and needs to be clearly communicated to the pathologist.
  
  
• For resection specimens requiring decalcification, optimal decalcification is a balance between preservation of histomorphology and timeliness. Decalcification end-point testing requires experienced laboratory technical staff with optimised standard operating procedures. Decalcification may take several days or weeks. If necessary, a provisional report on the soft tissue components of the specimen may be issued for adjuvant treatment planning purposes.
  
  
• Orientate neck dissection specimens and clearly label with the nodal groups indicated.
  
  
• When required, pre-arrange frozen sections for intraoperative margin assessment with the histopathology department. The indications of frozen sections for diagnosis are highly limited and its routine use is discouraged.

HPV, EBV, PD-L1, and molecular testing

• p16 immunohistochemistry is a widely accepted surrogate marker for HPV expression in oropharyngeal squamous cell carcinoma and has implications on staging and prognosis. This should be undertaken on all oropharyngeal squamous cell carcinomas.

• For cases positive with p16 immunohistochemistry undertake an accompanying HPV specific test in the form of PCR or in situ hybridization depending on local practice / access to testing.

• Perform p16 immunohistochemistry on biopsies of neck metastases from squamous carcinomas of unknown primary. Routine p16 and HPV testing is not recommended for head and neck SCC outside the oropharynx but can be considered in cases where there is reasonable potential diagnostic or therapeutic implications (e.g. uncommon variants of established disease entities, emerging new entities and primary tumour from another subsite overlapping with oropharynx).

• Undertake EBV on all suspected primary nasopharyngeal carcinomas and neck metastases from carcinomas of unknown primary in which primary nasopharyngeal cancer is possible.

• Undertake the PD-L1 (programmed death-ligand 1) testing only on cases requested by the MDT following clinical assessment of suitability for immunotherapy. Diagnostic validation following a period of training is required prior to combined percentage score and tumour percentage score reporting. Because inter-observer variation is recognised, it is prudent that a combined percentage score or tumour percentage score close to the 1 per cent cut-off be the consensus scored by two pathologists.

• Access to accredited molecular testing facilities is essential. Ensure tissue preparation and transfer between cellular and molecular pathology laboratories adheres to standard operating procedures. Gene mutation, rearrangement, amplification and deletion studies are important in some salivary gland, sinonasal neoplasms, carcinomas with unknown primary, or when the nature of malignancy is unclear. A directory for genomic tests under NHS Scotland and NHS England describes the available tests. Interpret all molecular testing results in the context of clinical, histomorphological and immunohistochemical findings, and integrated into the final pathology report.